We propose to establish the Columbia-Presbyterian AIDS Clinical Trials Unit which will include a subunit site at Harlem Hospital Center. The upper Manhattan region of New York City served by these two institutions and their satellite ambulatory care facilities is densely populated by black and Hispanic populations afflicted by poverty, drug abuse and extraordinarily high rates of HIV infection and AIDS. The Columbia- Presbyterian ACTU will be based within the established AIDS treatment and research units of the component institutions to assure maximum access to trials especially for their minority poor and female patients. The overall goal is to provide coordinated and comprehensive social, psychological and medical services simultaneously with research activities so that our patients do not have to make a choice between access to advanced AIDS treatments and everyday basic needs such as housing, food and child care. The current AIDS inpatient, ambulatory care and research programs at the Columbia-Presbyterian Medical Center and Harlem Hospital serve a combined population eligible for clinical trials which has the following characteristics: approximately 1500 active patients, one third each with AIDS, AIDS-related complex and asymptomatic HIV infection; 90% of black or Hispanic ethnic origin; and 40% women. The Columbia-Presbyterian ACTU will draw together an extensive array of clinical and research resources at the College of Physicians and Surgeons of Columbia University and its affiliates Presbyterian and Harlem Hospitals. Close collaboration with Columbia's Pediatric ACTU and Women-Infants Transmission Study (WITS) will facilitate access to treatment trials for the HIV infected women involved in these programs. The existing core laboratories for flow cytometry and virology which were established for these programs will be incorporated into the proposed adult ACTU to maximize efficiency and enhance scientific productivity of all the AIDS programs involved. Neurology will be a special area of concentration for the Columbia- Presbyterian ACTU. Neurologists at Columbia who will play a central role in ACTU activities have developed expertise and resources related to neurobehavioral features of HIV infection in several demographic subgroups including Hispanics, blacks, women and Iv drug users through the NIMH-sponsored HIV Center for Clinical and Behavioral Studies. A Core Pharmacology laboratory is proposed which will be based in a Columbia facility experienced in large volume multi-center trials as well as innovative methodologic development. Developmental research proposals are closely linked to major clinical concerns and are based on strong current research efforts in each area: Developmental virology will focus on the molecular pathogenesis of HIV reverse transcriptase resistance to dideoxynucleosides; Developmental Immunology will evaluate in vitro immune functional assays as surrogate markers for antiretroviral drug efficacy; Developmental Pharmacology will examine the cellular pharmacology and therapeutics of intracellular infections in AIDS, especially M. Tuberculosis; and Developmental Research in Endocrinology will evaluate the contribution of endocrine factors in the HIV wasting syndrome.